Atrasentan in Patients With IgA Nephropathy
Purpose
The ALIGN Study is a phase 3, double-blind, placebo-controlled study to compare the efficacy and safety of atrasentan to placebo in patients with IgA nephropathy (IgAN) at risk of progressive loss of renal function.
Conditions
- IgA Nephropathy
- Immunoglobulin A Nephropathy
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Biopsy-proven IgA nephropathy. - Receiving a maximally tolerated dose of RAS inhibitor therapy (ACEi or ARB) that has been stable for at least 12 weeks. Exceptions from this requirement will be made for subjects who are unable to tolerate RAS inhibitor therapy. - Total urine protein ≥1 g/day as measured via 24-hour urine collection by central laboratory at Screening. - eGFR of at least 30 mL/min/1.73 m2 at Screening based on the CKD-EPI equation. - Willing and able to provide informed consent and comply with all study requirements. - SGLT2i Stable Stratum Only - Receiving a stable dose of an SGLT2i (per Investigator choice) in addition to a maximally tolerated and optimized dose of a RAS inhibitor that has been stable for at least 12 weeks prior to Screening.
Exclusion Criteria
- Current diagnosis with another chronic kidney disease, including diabetic kidney disease. - History of kidney transplantation or other organ transplantation. - Use of systemic immunosuppressant medications, such as steroids, for more than 2 weeks in the past 3 months. - Blood pressure above 150 mmHg systolic or 95 mmHg diastolic as evaluated by the Investigator. - Known history of heart failure or a previous hospital admission for fluid overload. - Clinically significant history of liver disease as assessed by the Investigator. - Hemoglobin below 9 g/dL as measured by the Investigator or prior history of blood transfusion for anemia within the past 3 months. - Malignancy within the past 5 years. Exceptions to this criteria include nonmelanoma skin cancer and curatively treated cervical carcinoma in situ. - For women, pregnancy, breast feeding, or intent to become pregnant during the study. and at least 1 month afterward. - For men, intent to father a child or donate sperm during the study. - Have received any investigational agent or approved treatment for IgAN (other than a RAS inhibitor) including SGLT2i (except for subjects in the SGLT2i stable stratum) within 1 month (or 5 half-lives of the agent, whichever is longer) prior to Screening. If the investigational agent is a cytotoxic or immunosuppressive agent then this washout period is 6 months.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
- Masking Description
- Double-blind
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Atrasentan |
Once daily oral administration of 0.75 mg atrasentan for 132 weeks |
|
|
Placebo Comparator Placebo |
Once daily oral administration of placebo for 132 weeks |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Chinook Therapeutics U.S., Inc.
Study Contact
Detailed Description
Approximately 320 patients with biopsy-proven IgAN will be randomized to receive 0.75 mg atrasentan or placebo daily for 132 weeks. Subjects receive a maximally tolerated and stable dose of a RAS (renin-angiotensin system) inhibitor [such as angiotensin converting enzyme inhibitor (ACEi) or angiotensin-receptor antagonist (ARB)] as part of standard of care. An exception will be made for subjects who are unable to tolerate RAS inhibitor therapy. Additional subjects receiving a stable dose of SGLT2i will be enrolled to the study. Enrollment in this SGLT2i stable stratum will be in accordance with local regulations in regions that prescribe SGLT2i and will be independent of the 320 subjects enrolled for the primary and secondary analyses. The primary objective of the study is to evaluate the effect of atrasentan versus placebo on proteinuria as measured by UPCR. Secondary and tertiary objectives include evaluating the change in kidney function over time as measured by eGFR, safety and tolerability, as well as quality of life. Subjects will have assessments of safety and efficacy over 2 ½ years. To facilitate study participation over this time period, where allowed by local regulations, options for remote study visits using telemedicine and home health may be offered. Subjects who complete treatment through Week 132 and complete the double-blinded portion of the study may be eligible to enroll in the open label extension of the study.